Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology. Hereditary susceptibility to sarcoidosis is suggested by reports of familial clustering and a higher prevalence in certain ethnic groups, particularly African-Americans. Candidate genes for the granulomatous inflammatory disorders, Blau syndrome and Crohn's disease have been localized to the centrometric region of chromosome 16. We therefore investigated whether this region is also involved in sarcoidosis. Using a sample of 35 African-American affected sibling pairs, we found no evidence of linkage in this general region, and could exclude from it a dominant gene with relative risk < 5, or a recessive gene with relative risk < 3,causing sarcoidosis. In particular, we concluded that the Blau syndrome gene does not have a major effect on sarcoidosis susceptibility. We plan to test for association of sarcoidosis with markers for other candidate genes and to perform a segregation analysis in order to test simultaneously for possible environmental risk factors and genetic mechanisms of disease transmission. This study is ongoing.